Spain

This proposal seeks to discover a novel process for staging disease based upon the molecular characteristics of cancer stem cells. We propose to use physical techniques and inherent physical phenomena of the samples as the basis to investigate a new realm for molecular pathology and also to use these techniques as an aid to current pathology.The research is needed into the fundamental differences between the associated model cell lines to enable the elucidation of biochemical markers to aid histopathology. The techniques are very complimentary - SIMS and MIMS are mass spectral techniques and ATR-IR and Raman are spectroscopic. Utilising these techniques we will cover the full range of elemental (isotopic), molecular and macromolecular information. This will provide translational molecular markers which can be identified by more clinically routine methods e.g staining for chemicals elucidated by this study.

I propose to use modern high-throughput sequencing technologies coupled with ecological data to address one of the major questions in speciation research: the importance of gene flow in speciation. Speciation is the fundamental route to the generation of new species biodiversity. However, the importance of gene flow in speciation, and the role of selection in this process are not well understood. Gene flow can have two diametrically opposite influences on speciation: 1) Gene flow is an obvious hindrance to speciation as it will tend to break down co-adapted gene combinations and homogenize populations. Recent theoretical papers conceptualise the progress of species divergence in a four-phase model of islands of divergence amidst a sea of gene flow. While appealing, empirical support of this theoretical model of speciation remains elusive. 2) In some cases gene flow between taxa could trigger the formation of new species in a process known as hybrid speciation. However, there are few convincing examples of hybrid speciation, particularly among animals. I will investigate these two effects of gene flow on speciation in Heliconius. Neotropical Heliconius butterflies have long been a model system for studying speciation owing to the the presence of taxa representing the entire speciation continuum from freely hybridizing races differing in wing patterning, through sympatric species that occasionally hybridize in nature, to fully reproductively isolated species. With the publication of the first Heliconius genome sequence, Heliconius now provides one of the few systems suited for comprehensively studying the importance of gene flow in speciation. The proposed research focuses on three Heliconius species: H. elevatus, H. pardalinus and H. melpomene. My recent work has demonstrated the introgression of colour pattern genes between the species H. melpomene and H. elevatus. H. elevatus is genetically very closely related to H. pardalinus, but the two are distinct species with largely overlapping distributions and known differences in behaviour. Preliminary data suggest that the genome of H. elevatus is of hybrid origin, comprising H. melpomene colour pattern genes embedded in a background of H. pardalinus. I will gather whole genome sequence data and carry out ecological field experiments on races of H. elevatus and its two putative parental species, H. pardalinus and H. melpomene. These resulting data will allow us to test hypotheses on the importance and extent of gene flow in speciation. I have four main objectives: 1) My taxon sampling will allow empirical testing of the islands-of-divergence hypothesis of speciation with gene flow. 2) I will genetically map traits responsible for the early stages of speciation in H. elevatus and H. pardalinus. 3) The experimental design will allow rigorous testing of whether H. elevatus formed as a result of hybrid speciation. 4) I will test whether H. elevatus was formed from a single or multiple introgression events from different races of H. melpomene. Speciation is a basic evolutionary process that shapes all ecosystems, and the findings of this research will add significantly to our understanding of the genomic processes underlying the formation of new species.

What is the most effective way to slow deforestation and forest degradation? How can we best increase incomes from collection of non-timber forest products? Can education and information provision lead to real changes in behavior that better protects ecosystem services? After decades of attempts to better protect Amazonian forests and the ecosystem services that they provide, we still have no idea what the answers are to these questions. Further, notwithstanding the importance of ecosystem services, we have little evidence about which policy interventions can best ensure service provision and alleviate poverty. A fundamental need is thus for the development of 'program evaluation' methods in order to test policy or intervention effectiveness. In mid-altitude Bolivia, as in many parts of the developing world, agricultural decisions generate negative environmental externalities, reducing the quality and quantity of environmental service provision. Forest degradation, often associated with extensive cattle grazing, diminishes water quality and quantity and increases risks associated with landslides and flooding. There is a global and local interest in maintaining these upper Amazonian watershed forests both for their role in mitigating climate change, but also because their conservation will help local communities adapt to climate change through the maintenance of dry season water supplies. Despite the importance of these ecosystems for local poverty alleviation, local communities continue to graze more cattle than the carrying capacity of the forests, thus creating a tragedy of the commons in which deforestation, water pollution and flooding increase, and human welfare suffers. Our proposed research will explore alternative mechanisms for behavior change to mitigate the negative externalities that result from forest degradation. Our first hypothesis is that by providing targeted local information, or otherwise building local institutional capacity, we can lower collective action barriers at the community level, which will allow for locally imposed incentives through sanctions or positive compensation. As an alternative hypothesis, external donors, through direct payments, may better provide such incentives for improved grazing practices (i.e. a form of payments for environmental services). A rigorous experimental design will allows us to identify generalisable relationships between the provision of targeted information and financial incentives and resulting behavioral and biophysical outcome measures. By phasing in payments in the second year of the project, we will also observe the interaction between collective action and externally provided incentives. Although the list of activities sounds relatively esoteric, the implications of this research will be profound. We will develop and refine the program evaluation tools that are most appropriate for evaluations of ecosystem service provision, and then provide the first robust experimental analysis of what works for environmental service delivery and poverty alleviation and why. Our research will show that if a donor has, e.g. £500,000 to spend on climate change adaptation, whether it will it be most efficient for them, in terms of CO2 sequestered, water supplies protected, or livelihoods enhanced, to invest in local capacity building, information provision or direct payments schemes.

Three quarters of crop species depend on pollinators, but the service they provide is under increasing threat from climate change. Declines in pollinators are predicted to have negative impacts on human health as key dietary micronutrients in insect pollinated crops such as vitamin A and folate are lost from the diet. This "hidden hunger" is predicted to cause significant global health burdens. Climate change is already affecting pollinators, for example, the geographic range of bumblebees is shrinking as their southern range moves northwards, the synchrony between flowering plants and their pollinators is being disrupted and climate change is predicted to decrease bee species richness by 8-18% in some areas. Pollinator loss disproportionately harms developing countries, as they are both less resilient to yield drops and more reliant on the micronutrients found in small-scale pollinator-dependent crops. Providing population-wide vitamin supplementation is neither practical nor sustainable in remote parts of the world; instead, diversifying the diet by increasing access to micronutrient-rich fruits, vegetables and legumes could provide a solution. Fortunately, pollinator declines can be reversed, at least locally. Moreover, if the effect of climate change on pollinators is understood, habitat management can be used to mitigate against its effects. There is evidence of climate change, pollinator declines and micronutrient deficiency in our focal country Nepal and our research vision has four components: 1) to predict the effect of climate change on crop pollinators in Nepal; 2) to predict the ensuing impact on crop production and micronutrient intake; 3) run a field experiment to test the resilience of insect pollinated crops to climate change; 4) develop a policy and education package to mitigate the effects of climate change on crop pollination and micronutrient intake. Working with health professionals in Nepal, our international team of natural scientists and health scientists will provide information and innovative solutions for an understudied impact of climate change on human health.